title: Effects of nonsteroidal anti-inflammatory drugs on the bronchial hyperresponsiveness of middle-aged male smokers.
abstract: Bronchial hyperresponsiveness (BHR) in smokers is believed to be a consequence of airway wall inflammation. We have examined the effects of treatment with nonsteroidal anti-inflammatory drugs (NSAID) on BHR to inhaled histamine, measured as the provocative concentration reducing forced expiratory volume in one second (FEV1) by 20% (PC20), in middle-aged male cigarette smokers in two separate double-blind, placebo-controlled, cross-over trials. Baseline FEV1 in these smokers ranged from 41-117% predicted values. In the first study 15 men (mean age 58 yrs, FEV1 2.20 l) were examined before and one hour after a single dose of 1.2 g aspirin. There was no significant change in PC20 (geometric mean 1.88 mg.ml-1 pre-aspirin, 1.89 mg.ml-1 post-aspirin) or baseline FEV1 and we observed no tachyphylaxis to the effects of inhaled histamine at one hour after placebo. In the second study 10 men (mean age 60 yrs, FEV1 2.53 l) were examined before and after three days' treatment with the NSAID flurbiprofen 50 mg t.d.s. Baseline PC20 was higher in this group than in the first study. There was no relationship between the excretion of urinary thromboxane metabolites and the intensity of BHR under baseline conditions; flurbiprofen greatly reduced the urinary excretion of thromboxane metabolites, but baseline FEV1 was not altered. Analysis of change in PC20 was complicated by a difference in baseline PC20 before the two treatments, but treatment with flurbiprofen did not significantly attenuate BHR. The results suggest that thromboxane or other cyclo-oxygenase products of arachidonic acid metabolism do not play an important role in the short-term maintenance of BHR to histamine in middle-aged male cigarette smokers.
authors.affiliation: Dept of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
authors.forename: T K
authors.initials: TK
authors.lastname: Lim
authors.forename: N C
authors.initials: NC
authors.lastname: Turner
authors.forename: A
authors.initials: A
authors.lastname: Watson
authors.forename: H
authors.initials: H
authors.lastname: Joyce
authors.forename: R W
authors.initials: RW
authors.lastname: Fuller
authors.forename: N B
authors.initials: NB
authors.lastname: Pride
mesh_terms: D000368:Aged; D000403:Airway Resistance / Q000187:drug effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D004311:Double-Blind Method; D005480:Flurbiprofen / Q000008:administration & dosage / Q000494:pharmacology; D005541:Forced Expiratory Volume / Q000187:drug effects; D006632:Histamine; D006801:Humans; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000503:physiopathology*; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000652:urine
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013929:Thromboxane B2; D005480:Flurbiprofen; D006632:Histamine; D001241:Aspirin